JP2012519484A5 - - Google Patents

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JP2012519484A5
JP2012519484A5 JP2011552950A JP2011552950A JP2012519484A5 JP 2012519484 A5 JP2012519484 A5 JP 2012519484A5 JP 2011552950 A JP2011552950 A JP 2011552950A JP 2011552950 A JP2011552950 A JP 2011552950A JP 2012519484 A5 JP2012519484 A5 JP 2012519484A5
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一以上のマイクロＲＮＡ応答要素（ＭＲＥ）配列を含む組換えインフルエンザウイルスを含む組成物。   A composition comprising a recombinant influenza virus comprising one or more microRNA response element (MRE) sequences. 一以上のＭＲＥ配列は、一以上のインフルエンザウイルス遺伝子のコード領域内に挿入されている、請求項１に記載の組成物。   2. The composition of claim 1, wherein the one or more MRE sequences are inserted within the coding region of one or more influenza virus genes. 一以上のＭＲＥ配列は、人工的に作出されたインフルエンザウイルスの３’ＵＴＲ内に挿入されている、請求項１に記載の組成物。   2. The composition of claim 1, wherein the one or more MRE sequences are inserted within the 3'UTR of an artificially generated influenza virus. ＭＲＥは、種特異的発現によって特徴付けられるｍｉＲＮＡに対応する、請求項１に記載の組成物。   The composition of claim 1, wherein the MRE corresponds to a miRNA characterized by species-specific expression. ＭＲＥは、ワクチン接種を必要とする動物のインフルエンザ標的細胞では高度に発現するが、発育鶏卵内でインフルエンザウイルス増殖が生じる領域では発現しないか又は発現が非常に低レベルであるｍｉＲＮＡに対応する、請求項４に記載の組成物。 MREs are highly expressed in influenza target cells of animals in need of vaccination but correspond to miRNAs that are not expressed or have very low levels of expression in the region where influenza virus growth occurs in the developing chicken egg. Item 5. The composition according to Item 4 . ＭＲＥは、組織特異的発現又は細胞特異的発現によって特徴付けられるｍｉＲＮＡに対応する、請求項１に記載の組成物。   2. The composition of claim 1, wherein the MRE corresponds to an miRNA characterized by tissue specific expression or cell specific expression. ＭＲＥは、ワクチン接種を必要とする動物のインフルエンザ標的細胞では高度に発現するが、ワクチン作出に用いる細胞株では発現しないか又は発現が非常に低レベルであるｍｉＲＮＡに対応する、請求項６に記載の組成物。 MRE is highly expressed in animal influenza target cells in need of vaccination, or expression not expressed correspond to miRNA very low levels in cell lines used in vaccine production, according to claim 6 Composition. ＭＲＥは、ｍｉＲ−３４及びｍｉＲ−９３から成る群から選択されるｍｉＲＮＡに対応する、請求項１に記載の組成物。 MRE corresponds to miRNA selected from the group consisting of miR-34 and miR-93, A composition according to claim 1. ＭＲＥは、ｍｉＲ−１６、ｍｉＲ−１７、ｍｉＲ−１９、ｍｉＲ−２５、ｍｉＲ−９２、ｍｉＲ−１４２、ｍｉＲ−２２２、ｍｉＲ−１４９、ｍｉＲ−１９７７、ｍｉＲ−１８１ｂ−２、ｍｉＲ−１２５９及びｍｉＲ−１９７８から成る群から選択されるｍｉＲＮＡに対応する、請求項１に記載の組成物。MRE is miR-16, miR-17, miR-19, miR-25, miR-92, miR-142, miR-222, miR-149, miR-1977, miR-181b-2, miR-1259 and miR. The composition of claim 1 corresponding to a miRNA selected from the group consisting of -1978. ＭＲＥは、配列５’−ＵＧＧＣＡＧＵＧＵＣＵＵＡＧＣＵＧＧＵＵＧＵ−３’（配列番号５）を有するｍｉＲ−３４及び配列５’−ＣＡＡＡＧＵＧＣＵＧＵＵＣＧＵＧＣＡＧＧＵＡＧ−３’（配列番号７）を有するｍｉＲ−９３から成る群から選択されるｍｉＲＮＡに対応する、請求項８に記載の組成物。 MRE can correspond to miRNA selected from the group consisting of miR-93 having the sequence 5'-UGGCAGUGUCUUAGCUGGUUGU-3 'miR- 34 and SEQ 5'-CAAAGUGCUGUUCGUGCAGGUAG-3 (SEQ ID NO: 5)' (SEQ ID NO: 7) The composition according to claim 8 . ＭＲＥは、配列５’−ＵＡＧＣＡＧＣＡＣＧＵＡＡＡＵＡＵＵＧＧＣＧ−３’（配列番号１）を有するｍｉＲ−１６、配列５’−ＣＡＡＡＧＵＧＣＵＵＡＣＡＧＵＧＣＡＧＧＵＡＧ−３’(配列番号２）を有するｍｉＲ−１７、配列５’−ＵＧＵＧＣＡＡＡＵＣＵＡＵＧＣＡＡＡＡＣＵＧＡ−３’（配列番号３）を有するｍｉＲ−１９、配列５’−ＣＡＵＵＧＣＡＣＵＵＧＵＣＵＣＧＧＵＣＵＧＡ−３’（配列番号４）を有するｍｉＲ−２５、配列５’−ＵＡＵＵＧＣＡＣＵＵＧＵＣＣＣＧＧＣＣＵＧ−３’（配列番号６）を有するｍｉＲ−９２、配列５’−ＵＧＵＡＧＵＧＵＵＵＣＣＵＡＣＵＵＵＡＵＧＧＡ−３’（配列番号１４１）を有するｍｉＲ−１４２、配列５’−ＡＧＣＵＡＣＡＵＣＵＧＧＣＵＡＣＵＧＧＵ−３’（配列番号１４２）を有するｍｉＲ−２２２、配列５’−ＵＣＵＧＧＵＣＣＧＵＧＵＣＵＵＣＡＣＵＣＣＣ−３’（配列番号１４３）を有するｍｉＲ−１４９、配列５’−ＧＡＵＵＡＧＧＧＵＧＣＵＵＡＧＣＵＧＵＵＡＡ−３’（配列番号１４４）を有するｍｉＲ−１９７７、配列５’−ＡＡＣＡＵＵＣＡＵＵＧＣＵＧＵＣＧＧＵＧＧＧＵ−３’（配列番号１４５）を有するｍｉＲ−１８１ｂ−２、配列５’−ＡＵＡＵＡＵＧＡＵＧＡＣＵＵＡＧＣＵＵＵＵ−３’（配列番号１４６）を有するｍｉＲ−１２５９、及び配列５’−ＧＧＵＵＵＧＧＵＣＣＵＡＧＣＣＵＵＵＣＵＡ−３’（配列番号１４７）を有するｍｉＲ−１９７８から成る群から選択されるｍｉＲＮＡに対応する、請求項９に記載の組成物。MRE is miR-16 having the sequence 5'-UAGCAGCACGUAAAAUAUUGCG-3 '(SEQ ID NO: 1), miR-17 having the sequence 5'-CAAAGUGCUUACAGUGCAGGUAG-3' (SEQ ID NO: 2), sequence 5'-UGUGCAAAUGUAUGA-3 (sequence number 1) MiR-19 having SEQ ID NO: 3), miR-25 having sequence 5′-CAUUGCACUUGUCUCGUGUCUGA-3 ′ (SEQ ID NO: 4), miR-92 having sequence 5′-UAUUGCACUUGUCCCGGCCUG-3 ′ (SEQ ID NO: 6), sequence 5 MiR-142 with '-UGUAGUGUUUCCUCUCUUUAUGGA-3' (SEQ ID NO: 141), sequence 5'-AGCUACAUUCUGGCUACUGUGU-3 '(SEQ ID NO: 142) ), MiR-149 having the sequence 5′-UCUGGUCCGUGUCUUCUCUCCC-3 ′ (SEQ ID NO: 143), miR-1977 having the sequence 5′-GAUUAGGGUCUGUAA-3 ′ (SEQ ID NO: 144), sequence 5′-AUGUGU MiR-181b-2 having -3 ′ (SEQ ID NO: 145), miR-1259 having sequence 5′-AUAUAUGAUGACCUUAUGCUUUU-3 ′ (SEQ ID NO: 146), and sequence 5′-GGUUUGGUCUCUGCUCUUCUA-3 ′ (SEQ ID NO: 147) 10. The composition of claim 9, corresponding to a miRNA selected from the group consisting of miR-1978 having. 請求項１〜１１のいずれか１項に記載の組成物を含むワクチン。A vaccine comprising the composition according to any one of claims 1 to 11. 動物においてインフルエンザ感染に対する防御免疫応答を誘導するために使用する、請求項１２に記載のワクチン。 13. A vaccine according to claim 12 for use in inducing a protective immune response against influenza infection in an animal . インフルエンザウイルスコード配列と、前記コード配列内に挿入された一以上のマイクロＲＮＡ応答要素（ＭＲＥ）配列とを含む単離核酸分子。   An isolated nucleic acid molecule comprising an influenza virus coding sequence and one or more microRNA response element (MRE) sequences inserted within the coding sequence. インフルエンザウイルスコード配列と、転写物の終止コドンとポリアデニル化部位との間に挿入された一以上のマイクロＲＮＡ応答要素（ＭＲＥ）配列を含む人工３’非翻訳領域（３’ＵＴＲ）とを含む単離核酸分子。   A single comprising an influenza virus coding sequence and an artificial 3 ′ untranslated region (3′UTR) containing one or more microRNA response element (MRE) sequences inserted between the stop codon and polyadenylation site of the transcript. Isolated nucleic acid molecule. ＭＲＥは、ｍｉＲ−３４及びｍｉＲ−９３から成る群から選択されるｍｉＲＮＡに対応する、請求項１４又は１５に記載の核酸分子。 MRE corresponds to miRNA selected from the group consisting of miR-34 and miR-93, nucleic acid molecule of claim 14 or 15. ＭＲＥは、ｍｉＲ−１６、ｍｉＲ−１７、ｍｉＲ−１９、ｍｉＲ−２５、ｍｉＲ−９２、ｍｉＲ−２２２、ｍｉＲ−１４９、ｍｉＲ−１９７７、ｍｉＲ−１８１ｂ−２、ｍｉＲ−１２５９及びｍｉＲ−１９７８から成る群から選択されるｍｉＲＮＡに対応する、請求項１４又は１５に記載の核酸分子。The MRE consists of miR-16, miR-17, miR-19, miR-25, miR-92, miR-222, miR-149, miR-1977, miR-181b-2, miR-1259 and miR-1978. 16. A nucleic acid molecule according to claim 14 or 15 corresponding to a miRNA selected from the group. ＭＲＥは、配列５’−ＵＧＧＣＡＧＵＧＵＣＵＵＡＧＣＵＧＧＵＵＧＵ−３’（配列番号５）を有するｍｉＲ−３４及び配列５’−ＣＡＡＡＧＵＧＣＵＧＵＵＣＧＵＧＣＡＧＧＵＡＧ−３’（配列番号７）を有するｍｉＲ−９３から成る群から選択されるｍｉＲＮＡに対応する、請求項１６に記載の核酸分子。 MRE can correspond to miRNA selected from the group consisting of miR-93 having the sequence 5'-UGGCAGUGUCUUAGCUGGUUGU-3 'miR- 34 and SEQ 5'-CAAAGUGCUGUUCGUGCAGGUAG-3 (SEQ ID NO: 5)' (SEQ ID NO: 7) The nucleic acid molecule according to claim 16 . ＭＲＥは、配列５’−ＵＡＧＣＡＧＣＡＣＧＵＡＡＡＵＡＵＵＧＧＣＧ−３’（配列番号１）を有するｍｉＲ−１６、配列５’−ＣＡＡＡＧＵＧＣＵＵＡＣＡＧＵＧＣＡＧＧＵＡＧ−３’(配列番号２）を有するｍｉＲ−１７、配列５’−ＵＧＵＧＣＡＡＡＵＣＵＡＵＧＣＡＡＡＡＣＵＧＡ−３’（配列番号３）を有するｍｉＲ−１９、配列５’−ＣＡＵＵＧＣＡＣＵＵＧＵＣＵＣＧＧＵＣＵＧＡ−３’（配列番号４）を有するｍｉＲ−２５、配列５’−ＵＡＵＵＧＣＡＣＵＵＧＵＣＣＣＧＧＣＣＵＧ−３’（配列番号６）を有するｍｉＲ−９２、及び配列５’−ＵＧＵＡＧＵＧＵＵＵＣＣＵＡＣＵＵＵＡＵＧＧＡ−３’（配列番号１４１）を有するｍｉＲ−１４２、配列５’−ＡＧＣＵＡＣＡＵＣＵＧＧＣＵＡＣＵＧＧＵ−３’（配列番号１４２）を有するｍｉＲ−２２２、配列５’−ＵＣＵＧＧＵＣＣＧＵＧＵＣＵＵＣＡＣＵＣＣＣ−３’（配列番号１４３）を有するｍｉＲ−１４９、配列５’−ＧＡＵＵＡＧＧＧＵＧＣＵＵＡＧＣＵＧＵＵＡＡ−３’（配列番号１４４）を有するｍｉＲ−１９７７、配列５’−ＡＡＣＡＵＵＣＡＵＵＧＣＵＧＵＣＧＧＵＧＧＧＵ−３’（配列番号１４５）を有するｍｉＲ−１８１ｂ−２、配列５’−ＡＵＡＵＡＵＧＡＵＧＡＣＵＵＡＧＣＵＵＵＵ−３’（配列番号１４６）を有するｍｉＲ−１２５９、及び配列５’−ＧＧＵＵＵＧＧＵＣＣＵＡＧＣＣＵＵＵＣＵＡ−３’（配列番号１４７）を有するｍｉＲ−１９７８から成る群から選択されるｍｉＲＮＡに対応する、請求項１７に記載の核酸分子。MRE is miR-16 having the sequence 5'-UAGCAGCACGUAAAAUAUUGCG-3 '(SEQ ID NO: 1), miR-17 having the sequence 5'-CAAAGUGCUUACAGUGCAGGUAG-3' (SEQ ID NO: 2), sequence 5'-UGUGCAAAUGUAUGA-3 (sequence number 1) MiR-19 having SEQ ID NO: 3), miR-25 having sequence 5′-CAUUGCACUUGUCUCGGUCUGA-3 ′ (SEQ ID NO: 4), miR-92 having sequence 5′-UAUUGCACUUGUCCCGGCCUG-3 ′ (SEQ ID NO: 6), and sequence MiR-142 having 5′-UGUAGUGUUUCCUACUUAUUGGA-3 ′ (SEQ ID NO: 141), sequence 5′-AGCUACAUUCUGCUCUUGGU-3 ′ (SEQ ID NO: 1) 42), miR-149 having the sequence 5'-UCUGGUCCGUGUCUUCACUCCCCC-3 '(SEQ ID NO: 143), miR-1977 having the sequence 5'-GAUUAGGGUCUCUAGAGGUGUUAA-3' (SEQ ID NO: 144), sequence 5'- MiR-181b-2 with AACAUUCAUUGCUGUCGGUGGGU-3 ′ (SEQ ID NO: 145), miR-1259 with sequence 5′-AUAUAUUGAUCUGUAGCUUUU-3 ′ (SEQ ID NO: 146), and sequence 5′-GGUUUGGUCUGUCUUCUGUCCU14 18. The nucleic acid molecule of claim 17, corresponding to a miRNA selected from the group consisting of miR-1978 having:
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